A Phase 2 interventional study of Dabrafenib 75 MG and Trametinib 2 MG in Thyroid Cancer, sponsored by Olivia Newton-John Cancer Research Institute. Recruiting at 9 sites in Australia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-31.
Sponsored by Olivia Newton-John Cancer Research Institute · Phase 2, Interventional, and Treatment
This prospective, multi-centre, open label, non-randomised phase II trial aims restore radioiodine sensitivity in patients with NRAS or BRAFV600E mutant refractory thyroid cancer.
Participants will be treated with Trametinib +/- Dabrafenib tyrosine kinase inhibitors for a period of 30 days, restoration of sensitivity will be monitored using 18F-FDG-PET \& I-124 PET imaging.
This is a prospective, non-randomised, multi-centre study which will be conducted at 10 sites around Australia.
Adult patients (18+ years) with radioiodine refractory differentiated thyroid cancer with BRAF V600E or NRAS mutant RECIST 1.1 evaluable tumours will be eligible to participate. .
All eligible patients will undergo a 18F-FDG PET/CT scan during the registration period (day -28), followed by T4 withdrawal and low iodine diet. T3 will be administered after T4 withdrawal and for up to 10 days prior to the 124I dose to minimise symptoms of hypothyroidism.
The first 124I dose will be administered orally at a dose of 40 MBq (1.08 mCi) on day -5 with a 18FDG-PET performed on the same day. Patients will then have 124I-PET imaging and bloods at 24 hrs (+/- 6 hrs) post-dose, with a second imaging time-point up until 120 hours post- 124I dose. The initial 124I study (pre-TKI) will serve as a baseline for the second 124I-PET (day 24, after 23 days of TKI), and demonstrate changes in NIS expression and radioiodine uptake as a result of TKI treatment.
Patients will then commence a total of 30 days of treatment with the MEK TKI trametinib (for NRAS mutant tumours) or the MEK and BRAF V600E TKI combination of trametinib and dabrafenib (for BRAF V600E mutant tumours). Patients will then have a further 18F-FDG PET/CT scan and 124I dose on day 23, and scans for dosimetry (124I-PET) at 24 hrs (+/- 6 hrs) post-dose (day 24), with a second imaging time-point up until 120 hours post-124I administration. If at least one lesion shows uptake on 124I scans consistent with > 20Gy / 6GBq (3.3Gy/GBq) 131I administered (based on the 24-hour scan), then 131I treatment will be administered on day 29. The dose of 131I administered will be fixed at 6 GBq (150 mCi) to allow for evaluation of dose response. TKI treatment will continue until the day after 131I treatment is given (total 30 days).
Follow-up staging (CT) will occur every 3 months for the first 24 months, then every 6 months until progression, and 18F-FDG PET at 6 and 12 months. Non-stimulated thyroglobulin (Tg) will also be measured at 3, 6, 9 and 12 months, and evaluated as a percentage change from baseline. QoL and health economic data will be collected in all patients going on study. Overall survival will be obtained by long-term follow-up. Central review of tumour mutations, 124I PET dosimetry, staging (RECIST) and 18F-FDG PET (PERCIST) will be performed.
785 studies on the registry are indexed under Thyroid Neoplasms; 204 are open to participants now.
This study's planned enrollment of 80 is above the median of 53 across 520 interventional studies indexed under Thyroid Neoplasms.
Browse Thyroid Neoplasms studies →Olivia Newton-John Cancer Research Institute is the lead sponsor of 14 studies on the registry; 7 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Radioiodine (at least one of):
Adequate haematological and biochemical parameters:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Prior to commencing interventional treatment, participants will commence a low iodine diet and undergo thyroxine withdrawal and commence T3 replacement from day -27. On day -5 they will receive an oral dose of 124I (40MBq/1.08 mCi) with imaging at 24 hours (+/-6) post dose and a second imaging assessment within 120 hours. Participants will receive Dabrafenib (oral, 150mg BD) and Trametinib (oral, 2mg OD) from day 1-30. A second oral dose of I124 will be administered at day 24 followed by imaging at the same interval as baseline. Participants achieving \>20Gy tumour uptake of I124 will be administered 6GBq (3.3Gy/GBq) 131I, I131 wb scan and SPECT/CT will be performed within 24 hours and at hospital discharge. Participants who do not achieve \>20Gy tumour update of I-124 will move into follow up. Follow up will occur every 12 weeks for 12 months.
Drug: Dabrafenib 75 MG · Drug: Trametinib 2 MG
Prior to commencing interventional treatment, participants will commence a low iodine diet and undergo thyroxine withdrawal and commence T3 replacement from day -27. On day -5 they will receive an oral dose of 124I (40MBq/1.08 mCi) with imaging at 24 hours (+/-6) post dose and a second imaging assessment within 120 hours. Participants will receive Trametinib (oral, 2mg OD) from day 1-30. A second oral dose of I124 will be administered at day 24 followed by imaging at the same interval as baseline. Participants achieving \>20Gy tumour uptake of I124 will be administered 6GBq (3.3Gy/GBq) 131I, I131 wb scan and SPECT/CT will be performed within 24 hours and at hospital discharge. Participants who do not achieve \>20Gy tumour update of I-124 will move into follow up. Follow up will occur every 12 weeks for 12 months.
Drug: Trametinib 2 MG
Refer arm description
Also known as: Tafinlar
Refer arm description
Also known as: Mekinist
Progression free survival as assessed by RECIST 1.1 criteria at 6 months in participants who proceed to I131 treatment
Radioiodine refractory thyroid cancer patients able to proceed to 131I treatment will be assessed by RECIST 1.1 criteria.
Time frame: At 6 months following day 1.
Progression free survival as assessed by RECIST 1.1 criteria at 12 months in participants who proceed to I131 treatment
Radioiodine refractory thyroid cancer patients able to proceed to 131I treatment will be assessed by RECIST 1.1 criteria.
Time frame: At 12 months following day 1.
Progression free survival as assessed by RECIST 1.1 criteria at 6 months in all participants and a control population (SELECT study)
To assess PFS by RECIST v1.1 at 6 in radioiodine-refractory thyroid cancer patients able to proceed to 131I treatment following TKI redifferentiation therapy, 1. compared to those who do not proceed to 131I treatment. 2. compared to a control population (from the SELECT study).
Time frame: At 6 months following day 1.
Progression free survival as assessed by RECIST 1.1 criteria at 12 months in all participants and a control population (SELECT study)
To assess PFS by RECIST v1.1 at 12 months in radioiodine-refractory thyroid cancer patients able to proceed to 131I treatment following TKI redifferentiation therapy, 1. compared to those who do not proceed to 131I treatment. 2. compared to a control population (from the SELECT study).
Time frame: At 12 months following day 1.
Objective response rate by RECIST 1.1 criteria in all treated participants
To assess objective response (CR/PR/SD) in all treated participants from time of enrolment until 18 months or PD.
Time frame: 0-18 months or at PD
Overall survival of treated participants
To confirm the overall survival of participants receiving treatment on study via Kaplan-Meier estimation.
Time frame: From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
Quantification of treatment related toxicities according to CTCAE V5.0
Quantification of treatment related toxicities according to CTCAE V5.0
Time frame: From day -27 until 30 days following last dose [up to max 60 days].
Quantification of radioiodine uptake in metastatic lesions before and after TKI treatment.
Quantification of radioiodine uptake in metastatic lesions before and after TKI treatment.
Time frame: From day -5 until day 30 on study.
Evaluation of response to treatment by percent change from baseline of non-stimulated thyroglobulin.
Evaluation of response to treatment by percent change from baseline of non-stimulated thyroglobulin.
Time frame: Day 0; 3, 6, 9, 12 months in participants without radiological progression.
Evaluation and comparison of quality of life as measured by response to EORTC-QLQ-C30 in participants on study.
Evaluation of QOL in participants who proceed to I131 treatment compared with participants who proceed to follow up only by EORTC-QLQ-C30. Scores are from 0-100 with participant reported quality of live improving with a higher score.
Time frame: Day -29, 1, 29; 3, 6, 9, 12 months.
Evaluation and comparison of QOL as measured by response to EQ-5D-5L in participants on study.
In participants who proceed to I131 treatment compared with follow up only by EQ-5D-5L. Five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems to extreme problems.
Time frame: Day -29, 1, 29; 3, 6, 9, 12 months.
Evaluation and comparison of QOL as measured by response to Kessler Psychological Distress Scale (K10) in participants on study.
In participants who proceed to I131 treatment compared with follow up only by responses to the Kessler Psychological Distress Scale (K10). This is a 10-item questionnaire yielding a global measure of distress based on questions about anxiety and depressive symptoms. 5 levels ranging from none of the time to all of the time, higher level responses correspond with greater reported distress.
Time frame: Day -29, 1, 29; 3, 6, 9, 12 months.
Plan to share: No
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Studies of the drug tested here: Dabrafenib
Olivia Newton-John Cancer Research Institute